An updated international consensus from the European Alliance of Associations for Rheumatology (EULAR) provides clarified guidance on the use of antirheumatic drugs in patients before, during, and after pregnancy. Developed by a multidisciplinary task force representing 13 countries, the 2024 recommendations replace the 2016 version and are based on a systematic literature review and structured consensus methodology. All recommendations were assigned a level of evidence and grade of recommendation using the Oxford Centre for Evidence-Based Medicine criteria and received high agreement scores (≥85% endorsement) among panel members.

Reproductive Planning and Pregnancy Management

Patients of reproductive age should receive early and regular counseling to prevent inadvertent exposure to teratogenic agents and to optimize pregnancy outcomes. Conception should occur during disease remission or low activity while the patient is receiving pregnancy-compatible therapy. If active disease persists, conception should be postponed and treatment adjusted accordingly.

Pregnancy-compatible conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) include:

• Hydroxychloroquine at doses up to 400 mg per day (preferred over chloroquine)

• Chloroquine

• Azathioprine (up to 2 mg/kg/d in patients with normal thiopurine metabolism)

• Mercaptopurine

• Cyclosporine

• Tacrolimus

• Sulfasalazine (up to 2 g/d, with folic acid)

• Colchicine (1–2 mg/d)

These agents have not been associated with an increased risk of congenital anomalies or adverse pregnancy outcomes (LoE: 2a/B–2c/C).

Contraindicated drugs due to known teratogenicity include methotrexate, mycophenolate, and cyclophosphamide. Recommended washout periods are:

• Methotrexate: 1–3 months

• Mycophenolate: 1.5 months

• Cyclophosphamide: 3 months

NSAIDs may be used intermittently during early and mid-pregnancy but should be discontinued after 28 weeks of gestation because of risks such as ductus arteriosus constriction and oligohydramnios. Ibuprofen is preferred due to its short half-life. Glucocorticoids such as prednisone and prednisolone are generally considered safe; however, daily doses should be limited to 5 mg or less when possible (level of evidence: 2a/B). Higher doses have been associated with adverse outcomes, including gestational diabetes, infections, and preterm birth.

For patients with severe or refractory maternal disease, additional options may include:

• Intravenous methylprednisolone pulses

• Intravenous immunoglobulin (IVIG)

• Sildenafil

• Continued use of compatible csDMARDs or biologic DMARDs (bDMARDs)

• In second or third trimester only: mycophenolate or cyclophosphamide may be considered in life-threatening cases

Biologic DMARDs and Vaccine Considerations

All TNF inhibitor (TNFi) bDMARDs—including infliximab, adalimumab, etanercept, golimumab, and certolizumab—may be used throughout pregnancy. Certolizumab, a PEGylated Fab fragment lacking the Fc region, has negligible placental transfer and does not affect the infant's vaccine schedule. In contrast, monoclonal IgG1 agents such as infliximab and adalimumab readily cross the placenta from gestational week 20 onward and may require adjustments to live infant vaccinations.

Specifically:

• BCG vaccine should be delayed for 6 months if in utero exposure to high-transferring TNFi agents occurred after gestational week 20.

• Rotavirus vaccine may be administered on schedule.

• Nonlive vaccines are considered safe for all exposed infants.

Non-TNFi bDMARDs—including abatacept, anakinra, belimumab, rituximab, secukinumab, tocilizumab, and ustekinumab—may also be used if clinically indicated, though supporting data are more limited (LoE: 4/C–5/D). Agents lacking sufficient data (e.g., anifrolumab, guselkumab, mepolizumab, risankizumab) should be avoided unless no safer options exist.

Lactation Considerations

The majority of csDMARDs, NSAIDs, and all bDMARDs are considered compatible with breastfeeding due to minimal transfer into breast milk and negligible oral bioavailability in infants. Recommended agents include:

• Hydroxychloroquine, azathioprine, sulfasalazine, colchicine

• Ibuprofen (preferred NSAID)

• Prednisone and prednisolone (short delay post high-dose IV methylprednisolone suggested: 2–4 hours)

Methotrexate at doses up to 25 mg per week, sildenafil, and bosentan may be considered when alternatives are lacking, although evidence is limited. Drugs that should be avoided during breastfeeding include cyclophosphamide, mycophenolate, leflunomide, Janus kinase inhibitors, and voclosporin.

Use in Male Patients

Most antirheumatic medications are not associated with impaired male fertility or adverse offspring outcomes and can be continued during conception planning. Compatible agents include:

• Methotrexate at doses up to 25 mg per week, mycophenolate, and leflunomide

• Hydroxychloroquine, sulfasalazine, azathioprine, colchicine

• NSAIDs, glucocorticoids, sildenafil

• TNFi and non-TNFi bDMARDs

Sulfasalazine may cause reversible impairment in sperm quality. If conception is delayed, discontinuation should be considered. Cyclophosphamide is associated with dose-related irreversible infertility, and sperm preservation should be discussed prior to initiation.

Implementation and Shared Decision-Making

EULAR noted the importance of shared decision-making and early multidisciplinary counseling. Treatment planning should weigh the risks of medication exposure against the risks of uncontrolled maternal disease, which itself is associated with adverse reproductive outcomes.

All recommendations were developed through a structured voting and consensus process and received a high level of agreement, with most receiving scores of 8 or higher out of 10 from at least 96% of voters. The authors acknowledged data limitations for newer agents and encouraged clinicians to refer to the full tables and references for detailed guidance.

Funding and Disclosures:
The task force received support from EULAR. Full author disclosures and methods are available in the published article.

Source: Annals of Rheumatic Diseases